Graphical analysis of laboratory data in the differential diagnosis of cholestasis: a computer-assisted prospective study.
Data on 15 laboratory analytes obtained in 145 prospectively investigated cholestatic patients with viral hepatitis, chronic intrahepatic cholestasis and extrahepatic biliary obstruction were submitted to a computer-based graphical evaluation using probabilistic test analysis. This revealed a marginal utility for alkaline phosphatase, gamma-glutamyltransferase and the direct/total bilirubin ratio at specific cut-off points for the exclusion of extrahepatic cholestasis (PVneg 90%-100%). Aspartate aminotransferase and alanine aminotransferase values with cut-off points at 200 U/l and 300 U/l, respectively, were powerful discriminators between acute viral hepatitis and the other disease categories, while lactate dehydrogenase, erythrocyte sedimentation rate and the ratios gamma-glutamyltransferase/alanine aminotransferase as well as total bilirubin/gamma-glutamyltransferase were useful at specific cut-off points indicating the absence of this diagnosis (PVneg 92%-100%). An aspartate aminotransferase/alanine aminotransferase ratio above 1.5 and serum gamma-globulin concentrations above 20 g/l strongly suggested cholestasis due to chronic parenchymal liver disease (PVpos 92% and 90%, respectively). This graphical approach to laboratory data analysis enhances the understanding of the interrelations between cut-off points and sensitivity, specificity and predictive values and also of the influence of disease prevalence on disease prediction. It also adds to present knowledge by demonstrating the clinical relevance of several readily available, albeit rarely utilized diagnostic analytes.


Profile Changes in the Soil Microbial Community When Desert Becomes Oasis.
The conversion of virgin desert into oasis farmland creates two contrasting types of land-cover. During oasis formation with irrigation and fertilizer application, however, the changes in the soil microbial population, which play critical roles in the ecosystem, remain poorly understood. We applied high-throughput pyrosequencing to investigate bacterial and archaeal communities throughout the profile (0-3 m) in an experimental field, where irrigation and fertilization began in 1990 and cropped with winter wheat since then. To assess the effects of cultivation, the following treatments were compared with the virgin desert: CK (no fertilizer), PK, NK, NP, NPK, NPKR, and NPKM (R: straw residue; M: manure fertilizer). Irrigation had a greater impact on the overall microbial community than fertilizer application. The greatest impact occurred in topsoil (0-0.2 m), e.g., Cyanobacteria (25% total abundance) were most abundant in desert soil, while Actinobacteria (26%) were most abundant in oasis soil. The proportions of extremophilic and photosynthetic groups (e.g., Deinococcus-Thermus and Cyanobacteria) decreased, while the proportions of R-strategy (e.g., Gammaproteobacteria including Xanthomonadales), nitrifying (e.g., Nitrospirae), and anaerobic bacteria (e.g., Anaerolineae) increased throughout the oasis profile. Archaea occurred only in oasis soil. The impact of fertilizer application was mainly reflected in the non-dominant communities or finer taxonomic divisions. Oasis formation led to a dramatic shift in microbial community and enhanced soil enzyme activities. The rapidly increased soil moisture and decreased salt caused by irrigation were responsible for this shift. Furthermore, difference in fertilization and crop growth altered the organic carbon contents in the soil, which resulted in differences of microbial communities within oasis.


Palliative treatment of colorectal cancer in Germany: cost of care and quality of life.
To estimate the costs of palliative care for colorectal cancer (CRC) from the perspective of German statutory health insurance and to measure the patients' quality of life (QoL) for a 2-year time period. A prospective observational multicentre study was carried out to estimate the direct costs of care over a 2-year period. Case report forms, medical records, and claims data were all applied to document medical and resource usage data in real-world settings. QoL was measured by using the Short Form-12 Health Survey. In total 101 patients (mean age 67.09 ± 11.13 years, 68 % male) from 12 different settings were included. The mean costs per patient during the 1st and 2nd years were calculated to be 42,361€ and 32,023€, respectively. Highest mean costs were calculated for the second quarter, which reached an amount of 12,900€ (95 % CI: 11,127€-14,673€). Mean physical summary scores and mean mental summary scores were 41.8 and 49.7, respectively. This is the first study assessing the costs of palliative care and the quality of life of patients with CRC in real-world health-care delivery in Germany. It could be shown that CRC treatment represents an enormous economic burden to the German health-care system. Increased efforts in promoting effective and efficient treatment options, or performance-based medication reimbursement schemes, might be helpful in reducing the costs.


Weight gain during pregnancy and placenta morphology: a prospective cohort study.
The aim of this study was to assess the association between maternal weight gain and placenta morphology in the complete placenta previa pregnancies. This was a prospective clinical cohort study. Pregnancy weight gain was defined as the difference between delivery and at first trimester. Morphological parameters, including placenta length, breadth, thickness, length-breadth, surface area, weight, and fetoplacental weight ratio, were direct measured delivery. Eighty-five women were included in this study. Maternal weight gain was 11.12 ± 3.95 kg. Placenta length, breadth, thickness, length-breadth, surface area, weight and fetoplacental weight ratio were 19.42 ± 1.97 cm, 18.29 ± 1.80 cm, 2.18 ± 0.38 cm, 1.13 ± 0.80 cm, 281.60 ± 57.23 cm2, 569.05 ± 118.77 g, and 4.88 ± 0.88, respectively. Correlation analysis showed that there was a positive correlation between maternal weight gain and placenta length (r = 0.261, p = 0.016), placenta breadth (r = 0.239, p = 0.028), and placenta surface area (r = 0.254, p = 0.019). In the linear regression model, maternal weight gain was significantly associated with placenta length [β (95% CI): 0.130 (0.025-0.236)], breadth [β (95% CI): 0.109 (0.012-0.205)], and surface area [β (95%CI): 3.677 (0.615-6.739)]. The results were still stable after adjusting for pre-pregnancy weight. Maternal weight gain in pregnancy was associated with placental length, placental breadth, and placental surface area in a complete placenta previa pregnancies. Considering the single center data, further studies are needed to recognize the significance of the association analyzed in our study.


[Integration of the Expanded Program on Immunization into primary health care: examples of Benin and Guinea].
Since 1986, two West African countries have been delivering immunizations within the framework of reorganized peripheral health systems. This revitalization is based on strategies which are implemented by an increasing number of African countries under the name "Bamako Initiative". It aims at providing universal access to a minimum package of maternal and child health priority interventions starting with immunizations, pre and perinatal care, oral rehydration for diarrhoea, treatment of malaria and acute lower respiratory infections. Within this package, immunization has been given high priority. Several strategies aimed at improving immunization coverage have been implemented: services have been reorganized so that any child or woman making contact with the health system receives immunization if needed. Health information systems have been revised so as to allow for active individual follow up and better management of health centre resources. Health staff have been given training in management and a biannual monitoring/microplanning process at health centre level has been introduced. The goal of monitoring is to enable health personnel to identify the obstacles to attaining optimum coverages with the priority interventions and to select locally appropriate corrective strategies. Health centres have also been provided with a motorcycle allowing for regular outreach activities. To cover the running costs of the services (mainly restocking of drugs, running and maintenance of the cold chain and the motorbike, and staff incentives), financial contribution from local communities have been sought through a fee-for-treatment system. Prices have been set at an affordable level by limiting the number of drugs to a minimal list purchased under generic names by international tendering procedures.(ABSTRACT TRUNCATED AT 250 WORDS)


SPECT reconstruction by simulated annealing.
The technique of simulated annealing has been introduced for reconstruction in single photon emission computed tomography (SPECT) of data from rotating gamma camera systems. This is a much used technique in fields other than medical imaging but has only been used for one previous medical imaging application by Barrett et al (1983). It is shown that for noiseless data, the method can give perfect quantitative results, even when photon attenuation is included in the problem. This is true whatever the object distribution. With noisy data, mean level quantitation is still achievable although image mottle is worse. This paper describes simulated annealing in the language of SPECT, paying particular attention to the computational tricks which are central to a practicable implementation. The results of many computer simulations are presented to show the potential power of the method. A short comparison with other reconstruction techniques is made.


Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China.
H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China.


Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial carcinoma.
In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.


Impact of one year of shift work on cardiovascular disease risk factors.
The purpose of the study was to investigate whether the reported increased cardiovascular disease risk in shift workers could be explained by changes in cardiovascular risk factors. In a cohort of 239 shift and 157 daytime workers, 1-year changes in biological and lifestyle cardiovascular risk factors were monitored between the start of a new job and 1 year later. Both body mass index and low-density lipoprotein/high-density lipoprotein cholesterol ratio decreased significantly in shift workers compared with daytime workers (body mass index change: -0.31 and +0.13 kg/m; low-density lipoprotein/high-density lipoprotein ratio change: -0.33 and -0.13 respectively). Cigarettes smoked per day increased significantly in shift compared with daytime workers (+1.42 and -1.03, respectively). Therefore, only for smoking, an unfavorable change was observed. This may explain, at most, only a part of the excess cardiovascular disease risk reported in shift workers.


StarLight: a photonic neural network accelerator featuring a hybrid mode-wavelength division multiplexing and photonic nonvolatile memory.
This paper proposes StarLight, a low-power consumption and high inference throughput photonic artificial neural network (ANN) accelerator featuring the photonic 'in-memory' computing and hybrid mode-wavelength division multiplexing (MDM-WDM) technologies. Specifically, StarLight uses nanophotonic non-volatile memory and passive microring resonators (MRs) to form a photonic dot-produce engine, achieving optical 'in-memory' multiplication operation with near-zero power consumption during the inference phase. Furthermore, we design an on-chip wavelength and mode hybrid multiplexing module and scheme to increase the computational parallelism. As a proof of concept, a 4×4×4 optical computing unit featuring 4-wavelength and 4-mode is simulated with 10 Gbps, 15 Gbps and 20 Gbps data rates. We also implemented a simulation on the Iris dataset classification and achieved an inference accuracy of 96%, which is entirely consistent with the classification accuracy on a 64-bit computer. Therefore, StarLight holds promise for realizing low energy consumption hardware accelerators to address the incoming challenges of data-intensive artificial intelligence (AI) applications.


Influence of adenosinergic drugs on the epileptiform and neurotoxic effects of N-methyl-d-aspartate: comparison with the effects of MK801.
In the present paper, the influence of the adenosine receptor agonist N6-(l-2-phenylisopropyl)adenosine (L-PIA) and of the adenosine receptor antagonist caffeine on the epileptiform and neurotoxic effects of N-methyl-d-aspartate (NMDA) has been tested in rat hippocampal slices. Slice superfusion with 1 microM NMDA changed within 30 min the control CA1 field potentials into an epileptiform bursting in all experiments. Slice superfusion with 0.5-1 microM L-PIA or 50-100 microM caffeine plus 1 microM NMDA inhibited or potentiated, respectively, the CA1 epileptiform bursting duration with respect to a slice superfusion with 1 microM NMDA alone. Slice superfusion with 50-100 microM NMDA induced within a few minutes the appearance of short-lived (1-2 min) additional epileptiform population spikes, followed by an irreversible disappearance of the CA1 population spike. Slice superfusion with 50 microM of the NMDA antagonist dizocilpine (MK801) plus 50-100 microM NMDA prevented in all experiments the irreversible disappearance of the CA1 population spike with respect to a slice superfusion with 50-100 microM alone. Neither in a slice superfusion with 0.5-1 microM L-PIA plus 50-100 microM NMDA nor in a slice superfusion with 50-100 microM caffeine plus 50-100 microM NMDA did this effect occur. The results demonstrate that adenosine receptor ligands modulate the epileptiform but not the neurotoxic effects of NMDA.


[Clinical features of acute myocardial infarction inpatients in 26 level three class A Chinese medicine hospitals in China and the investigation of treatment].
To study the therapeutic state of acute myocardial infarction (AMI) inpatients in 26 level three class A Chinese medicine (CM) hospitals in China. The case report form (CRF) was designed and used in this study. Totally 1 094 AMI patients were recruited from 26 level three class A CM hospitals from January 2006 to December 2006. The onset, the heart function, complications, previous history, and CM syndrome types were observed in AMI patients. Treatment by Western medicine (WM), CM intravenous preparation, CM decoction, and Chinese patent medicine were also observed in AMI patients. Blood stasis syndrome (854 cases, 78.06%) and stagnant phlegm syndrome (470 cases, 42.96%) were dominated in the CM sthenia syndrome. Qi deficiency syndrome (683 cases, 62.43%) and Xin-yin deficiency syndrome (231 cases, 21.12%) were dominated in the CM asthenia syndrome. Totally 355 patients (32.45%) received reperfusion. Of them, 224 (20.48%) received percutaneous coronary intervention (PCI). The top 5 often used Western drugs covered aspirin (1001 cases, 91.50%), low molecular heparin (917 cases, 83.82%), blood lipids regulators (833 cases, 76.14%), ACEI/ARB (822 cases, 75.14%), and nitrates (773 cases, 70.66%). Totally 946 patients (86.47%) used CM intravenous preparations. The CM intravenous preparations with the use frequency more than 5% were sequenced as Shenmai Injection (520 times, 54.97%), Salvia miltiorrhizae preparations (305 times, 32.24%), sanchi preparations (185 times, 19.56%), Shenfu Injection (68 times, 7.19%), Scutellarin Injection (64 times, 6.77%), and Acanthopanax Injection (29 times, 3.07%). Totally 575 patients (52.56%) used CM decoction. The main therapeutic methods covered activating blood circulation therapy (477 cases), qi benefiting therapy (332 cases), and phlegm resolving therapy (303 cases). Commonly used recipes covered Shengmai Powder, Taohong Siwu Decoction, Gualou Xiebai Baijiu Decoction, Erchen Decoction, and Sijunzi Decoction. Totally 394 patients (36.01%) used Chinese patent medicines. Qi deficiency syndrome and blood stasis syndrome were dominated in AMI patients. Great achievements have taken place in AMI reperfusion treatment and standardized treatment in CM hospitals. CM are extensively used. Clinical studies on treating AMI by CM should be further strengthened.


Activation‑induced upregulation of MMP9 in mast cells is a positive feedback mediator for mast cell activation.
Activated mast cells are involved in the pathogenesis of allergic rhinitis (AR). As a member of the matrix metalloproteinase (MMP) family, MMP9 has been previously demonstrated act in a pro‑inflammatory manner. Mast cells regulate the activity of MMP9, and mast cells themselves have been reported to produce MMP9. However, to the best of our knowledge, the involvement of MMP9 in mast cell activation remains to be elucidated. The present study demonstrated an upregulation of MMP9 protein and mRNA expression levels in mast cells activated by phorbol ester and ionomycin. Phosphorylated ERK and AKT protein levels also markedly increased in activated mast cells, and inhibition of the ERK and AKT signaling pathways prevented the increase of MMP9 in activated mast cells. MMP9 was demonstrated to be involved in mast cell activation, since inhibition of MMP9 activity or expression inhibited mast cell activation. Furthermore, IL‑4 treatment reduced MMP9 upregulation in activated mast cells, and interference with IL‑4 signaling with an IL‑4 neutralizing antibody promoted MMP9 upregulation in activated mast cells. These results revealed a novel MMP9‑mediated mechanism underlying mast cell activation, thus providing novel ideas for AR therapy.


[Differing progress patterns in cancer of the uterine cervix and variant effects of adjuvant chemotherapy based on histological type].
Clinical features of 644 surgically treated cases of cancer of the uterine cervix were analyzed according to their histological type. Large cell non-keratinizing carcinomas (L) showed node metastasis proportional to the grade of invasion in the cervix, and the lowest recurrence rate. Small cell non-keratinizing carcinomas (S) tended to have widely spread metastasis from an early stage of the primary lesion. Lateral recurrence from metastatic foci was common in this type. Keratinizing carcinomas (K) were localized in the cervix until the primary tumor became enlarged to a certain size. Central recurrence from invasive foci in the surrounding tissue or organ occurred more often than lateral recurrence in this type. Metastasis pattern of pure adenocarcinomas (A) was similar to that of S, but recurrence was delayed. Adenosquamous carcinomas (AS) showed a similar metastasis pattern to that of K, but recurrence was rapid and the ratio high. Prophylactic maintenance chemotherapy with Tegafur (800 mg/day) or Carboquone (0.5 mg/day) was performed in 187 cases for a period of 2 years after surgery. The effect of maintenance chemotherapy depended on the histological type. A marked effect was obtained in the groups of S and A, in which no recurrence has appeared so far. The recurrence rate of L dropped to 1/5 that of the control. However, unsatisfactory results were shown in the groups of K and AS including the keratinizing cell component. It is of significance that maintenance chemotherapy showed the highest effectiveness in S and A on which conventional adjuvant therapy, i.e. postoperative radiotherapy, has had the least effect. This has led us to consider that a proper selection of adjuvant therapies would contribute toward improving the postoperative prognosis of patients with cancer of the uterine cervix.


Transplant Pulmonary Interventions: Translating Lung Transplant Interventions to Nontransplant Patients.
Roughly 10% of lung transplant recipients experience airway complications. Although the incidence has decreased dramatically since the first lung transplants were performed in the 1960s, airway complications have continued to adversely affect outcomes. Bronchoscopic interventions such as balloon dilation, airway stenting, and endobronchial electrocautery play an important role in ameliorating the morbidity and mortality associated with these complications. This review describes the array of bronchoscopic interventions used to treat airway complications after lung transplant and how these techniques can be used in nontransplant settings as well.


A review of prayer within the role of the holistic nurse.
Prayer is an integral component of the spiritual life of mankind. It is a two-way dialogue with God. Clients in crisis may need prayer for encouragement, comfort, and support. Holistic nurses may use prayer with clients to positively influence how they cope with anxiety relative to illness. Addressing the spiritual needs of clients is an important element of care and the use of prayer is supported by both informal client responses and scientific research. Additionally, the active use of prayer may provide added value and enrichment to the holistic nurse-client interaction.


Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii.
Forskolin is a unique structurally complex labdane-type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial production of forskolin relies exclusively on extraction from its only known natural source, the plant Coleus forskohlii, in which forskolin accumulates in the root cork. Here, we report the discovery of five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting the forskolin precursor 13R-manoyl oxide into forskolin and a diverse array of additional labdane-type diterpenoids. A minimal set of three P450s in combination with a single acetyl transferase was identified that catalyzes the conversion of 13R-manoyl oxide into forskolin as demonstrated by transient expression in Nicotiana benthamiana. The entire pathway for forskolin production from glucose encompassing expression of nine genes was stably integrated into Saccharomyces cerevisiae and afforded forskolin titers of 40 mg/L.


The effects of aerobic and resistance exercise on blood pressure in uncomplicated and at risk pregnancies: A systematic review and meta-analysis.
Regular exercise performed during pregnancy has been shown to reduce the risk of developing perinatal gestational hypertensive conditions. Further evidence on the exact parameters of exercise needed to explain these beneficial responses is required, within both uncomplicated and at-risk pregnancies. The aim of this systematic review and meta-analysis was to investigate the effects of aerobic and resistance exercise on blood pressure during pregnancy. Systematic review and meta-analysis. An online search of six search engines was conducted up to February 2023. Randomized controlled trials, quasi-experimental, cohort, and longitudinal studies were included. Studies included an acute exercise bout or intervention of land-based aerobic and/or resistance exercise during any trimester in uncomplicated and at-risk pregnancies. Outcomes included mean arterial pressure (MAP), or systolic blood pressure (SBP) and diastolic blood pressure (DBP). Following the removal of duplicates, 1538 articles were screened with 59 studies meeting the inclusion criteria for the review (randomized controlled trials (RCTs) n = 34, clinical trials n = 19, cohort n = 5 and cross-sectional n = 2), and 21 studies included in the meta-analysis. A random effects model was used with mean difference calculated in mmHg. Overall, there were no statistically significant effects of exercise on resting blood pressure (BP) outcomes in pregnant women with normal blood pressure compared to control/usual care populations following intervention (SBP mean diff -1.54 mmHg (favours intervention), p = 0.38; DBP mean diff -2.25 mmHg (favours intervention), p = 0.1; MAP mean diff -1.75 mmHg (favours intervention), p = 0.31). In at-risk pregnant women, both aerobic and combination exercise significantly reduced BP outcomes compared to control (SBP mean diff -3.91 mmHg, p < 0.01; DBP mean diff -2.9 mmHg, p = 0.01; MAP mean diff -2.38 mmHg, p = 0.01). Twenty-seven studies reported an acute increase in SBP and DBP during aerobic exercise, with no difference found between uncomplicated and at-risk pregnancies. Compared to usual care, aerobic and/or resistance exercise performed throughout uncomplicated pregnancy had no influence on blood pressure. Pregnant women with no diagnosed complications should be encouraged to exercise regularly due to the multitude of known benefits. In women who are at risk of, or diagnosed, with gestational hypertensive conditions during pregnancy, moderate to vigorous exercise during pregnancy improves blood pressure outcomes. Higher risk pregnancies may reduce their risk of future cardiovascular complications through regular exercise training during pregnancy. CRD42020159998.


Metal-assembling dendrimers with a triarylamine core and their application to a dye-sensitized solar cell.
A series of charge-separable and hole-transporting phenylazomethine dendrimers with a triarylamine core are prepared and evaluated for use as a charge separator in dye-sensitized solar cells (DSSCs). Triphenylamine with dendric phenylazomethine (TPA-DPA) is prepared by synthesizing up to five generations of dendrons using a convergent method. The resultant dendrimer has a rigid sphere structure similar to globular protein, with a hydrodynamic radius of 2.43 nm. Electrochemical oxidation of the TPA core reveals that the dendron units in the dendrimer have 0.35 of the attenuation factor (beta) in the electron transfer. Complexation of TPA-DPA with SnCl2 proceeds in stepwise fashion from the core to the terminal imine following the basicity gradient among imine groups in each dendron shell. DSSCs prepared by casting these dendrimers onto dye-sensitized TiO2 film exhibited a higher open-circuit voltage than the bare film through the suppression of back electron transfer. The generational growth of dendrons increases the radius of the dendrimer, resulting in a stronger association with I3- and higher open-circuit voltage with an increasing number of generations. Complexation with SnCl2 reduces the resistance of TPA-DPA and improves the fill factor. The energy conversion efficiency of the DSSC prepared using fifth-generation TPA-DPA is 21% higher than that for the bare film and, when complexed with SnCl2, provides a 34% improvement.


Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways.
Echinacea plant preparations are widely used in the prevention and treatment of common cold. However, so far no molecular mechanism of action has been proposed. We analyzed the standardized tincture Echinaforce and found that it induced de novo synthesis of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human monocytes/macrophages, but not TNF-alpha protein. Moreover, LPS-stimulated TNF-alpha protein was potently inhibited in the early phase but prolonged in the late phase. A study of the main constituents of the extract showed that the alkylamides dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (1/2), trienoic (3) and dienoic acid (4) derivatives are responsible for this effect. The upregulation of TNF-alpha mRNA was found to be mediated by CB2 receptors, increased cAMP, p38/MAPK and JNK signaling, as well as NF-kappaB and ATF-2/CREB-1 activation. This study is the first to report a possible molecular mechanism of action of Echinacea, highlighting the role of alkylamides as potent immunomodulators and potential ligands for CB2 receptors.


Incidental Durotomy Following Transforaminal Lumbar Interbody Fusion Performed with the Modified Wiltse Approach.
Incidental durotomy is an intraoperative complication that occurs in 3 to 27% of lumbar spine surgeries. It has been reported more commonly following revision spinal procedures. To investigate the frequency of incidental durotomy while performing transforaminal lumbar interbody fusion (TLIF) using the modified Wiltse approach. A secondary goal was to compare the incidence of durotomy in patients undergoing primary spine surgery with those undergoing revision surgery. A group of consecutive patients who had undergone (TLIF) in the last 10 years ending in 2015 were enrolled in the study. All patients underwent TLIF via the modified Wiltse approach that included a central midline skin incision, followed by a paravertebral blunt dissection of the paraspinal muscles to reach the transverse processes. The deep paravertebral dissection was done conservatively, one side at a time. Demographic and clinical data were collected when relevant to the comparison. The study cohort encompassed 257 patients: 200 primary cases and 57 revisions. The frequency of incidental durotomy was equal in both groups: 3.5% each (7/200 and 2/57). All durotomies were repaired primarily. No other immediate or late complications were observed during follow-up. The present study displays a limited incidence of durotomy in the primary interventions and to a lesser degree in the revisions, all of which had used a TLIF performed with the modified Wiltse approach. This procedure probably circumvented the need for further revisions.


Does 18F-FDG PET/CT change the surgical management of potentially resectable colorectal liver metastases?
Resectability assessment of patients with colorectal liver metastases is based on computed tomography and liver magnetic resonance imaging. Addition of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography has been recommended, but the impact of the added information remains unclear. The primary aim of this study was to determine how preoperative positron emission tomography/computed tomography changed management in patients with potentially resectable colorectal liver metastases. The secondary aim was to investigate whether findings on positron emission tomography/computed tomography correlated to metastatic disease in cases with extended surgery and influenced oncological outcomes. A retrospective observational study of the impact of adding positron emission tomography/computed tomography to conventional imaging in the surgical decision-making of colorectal liver metastases. All patients with colorectal liver metastases diagnosed by conventional imaging were included and assessed by a multidisciplinary team conference at Umeå University Hospital between June 2013 and December 2017. Eligibility criteria were all patients with potentially resectable colorectal liver metastases. Patients who underwent preoperative positron emission tomography/computed tomography in addition to conventional radiology were compared with those who underwent conventional imaging only. 151/220 patients underwent preoperative positron emission tomography/computed tomography. Findings on positron emission tomography/computed tomography changed the management in 10.6% of the patients. Eight patients were excluded from surgery after detection by positron emission tomography/computed tomography of extrahepatic disease. Eight patients underwent more extended surgery than initially planned due to positron emission tomography/computed tomography. Five of these positron emission tomography-positive resected sites were verified by pathology as metastatic disease. No difference in overall survival was seen following surgical resection in patients with and without a preoperative positron emission tomography/computed tomography. Preoperative positron emission tomography/computed tomography resulted in a changed surgical management in 10.6% of cases in a selected cohort.


Differential neuroendocrine and immune responses to acute psychosocial stress in women with type 1 bipolar disorder.
Bipolar disorder (BD) has been associated with immune imbalance, including lymphocyte activation and increased pro-inflammatory cytokines. Immune activation is part of stress response, and psychosocial stress has been implicated in the pathogenesis of psychiatric disorders. Here, we investigated the neuroendocrine and immune responses to acute psychosocial stress challenge in BD. Thirteen euthymic participants with type 1 BD and 15 healthy controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST. Lymphocytes were isolated and stimulated in vitro to assess lymphocyte activation profile, lymphocyte sensitivity to dexamethasone, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling by flow cytometry. Heart rate and salivary cortisol levels were monitored across the task. BD participants exhibited blunted stress responses as shown by reduced heart rate and salivary cortisol levels in comparison to healthy controls. BD was also associated with reduction in the percentage of regulatory T cells, but with expansion of activated T cells. When compared to controls, patients showed increased lymphocyte MAPK p-ERK and p-NF-κB signaling after the stress challenge, but exhibited a relative lymphocyte resistance to dexamethasone. In conclusion, stress-related neuroendocrine responses are blunted, associated with increased immune activation and lower sensitivity to glucocorticoids in BD. An inability in reducing NF-κB and MAPK signaling following TSST could be underlying the immune imbalance observed in BD.


Long Non-coding RNA RP11-395G23.3 Acts as a Competing Endogenous RNA of miR-124-3p to Regulate ROR1 in Anaplastic Thyroid Carcinoma.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with poor prognosis. However, the underlying mechanisms of ATC remain to be elucidated. Recently, increasing studies have focused on competitive endogenous RNA (ceRNA) to discover valuable biomarkers for the diagnosis of ATC. The present study identified 705 differentially expressed mRNAs and 47 differentially expressed lncRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. Additionally, an lncRNA/miRNA/mRNA network was constructed which included 1103 regulatory relations. The upregulation of RP11-395G23.3 in ATC cells was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In the loss of function assays, results suggested silencing of RP11-395G23.3 inhibited cell proliferation and induced cell apoptosis. Mechanically, RP11-395G23.3 could increase ROR1 via sponging miR-124-3p as a ceRNA. Moreover, ROR1 expression was decreased with the downregulation of RP11-395G23.3, but was rescued by the co-transfection of the miR-124-3p inhibitor in ATC cells. Our research suggested that the RP11-395G23.3/miR-124-3p/ROR1 axis potentially acted as a potential target for the diagnosis of ATC.


Optical imaging and tumor angiogenesis.
Tumor angiogenesis is essential for tumor growth and progression. Therefore, targeting tumor blood vessels is a promising approach for cancer therapy. Angiogenesis, the formation of blood vessels, is a multistep process, and strongly influenced by the microenvironment. There are no in vitro assays that can resemble this dynamic process in vivo. For this reason, animal models and imaging technologies are critical for studying tumor angiogenesis, identifying therapeutic targets as well as validating the targets. Non-invasive molecular imaging in animal models presents an unprecedented opportunity and ability for us to perform repetitive observations and analysis of the biological processes underlying tumor angiogenesis and tumor progression in living animals in real time. As we gain a better understanding of the fundamental molecular nature of cancer, these techniques will be an important adjunct in translating the knowledge into clinical practice. This important information may elucidate how the tumor blood vessels behave and respond to certain treatments and therapies.


Effects of treatment with chemotherapy and/or tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer.
There has been an increase in deaths from cardiovascular diseases following breast cancer therapy. Evidence has shown that this outcome is, in part, associated with cardiotoxicity induced by the chemotherapeutic drugs and the increase in oxidative stress. The aim of this study was to evaluate the effects of chemotherapy and hormone therapy with tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer.Thirty women were followed-up for 1 year and were divided into 3 groups according to the treatment protocol: women treated only with tamoxifen and clinical follow up for 12 months (Tam, n = 10); women treated only with chemotherapy for 6 months with clinical follow up for an additional 6-month period (Chemo, n = 10); and women who received chemotherapy for 6 months followed by a 6-month period only with tamoxifen therapy and clinical follow up (Chemo + Tam, n = 10). Analysis of the blood levels of cardiac troponin I (cTnI), advanced oxidation protein products (AOPP) and the activity of the plasmatic isoform of the antioxidant enzyme glutathione peroxidase (GPx) was performed before treatment (T0) and at 6 (T6) and 12 (T12) months after treatment.The Chemo group showed higher levels of cTnI (0.065 ± 0.006 ng/mL, P < .05) and AOPP (4.99 ± 0.84 μmol/L, P < .05) and reduced GPx activity (24.4 ± 1.1 nM/min/mL, P < .05) at T12 than the Tam group (cTnI: 0.031 ± 0.001 ng/mL; AOPP: 1.40 ± 0.10 μmol/L; GPx: 28.0 ± 0.7 nM/min/mL) and Chemo + Tam group (cTnI: 0.037 ± 0.002 ng/mL; AOPP: 2.53 ± 0.30 μmol/L; GPx: 29.5 ± 1.0 nM/min/mL).These data support the hypothesis that long-term oxidative stress after chemotherapy may have an impact on cardiovascular diseases and that tamoxifen has cardioprotective effects.


Hyperphosphorylation of CD20 in hairy cells. Alteration by low molecular weight B cell growth factor and IFN-alpha.
Hairy cell leukemia (HCL) is a B cell tumor affecting the pre-plasma stage of B cell differentiation. Hairy cells produce B cell growth factor (BCGF)-related growth factor(s) and we have previously shown that low mol wt (LMW)-BCGF-induced proliferation of hairy cells is inhibited in vitro and in vivo by IFN-alpha. We therefore suggested that this effect might contribute to the exquisite sensitivity of HCL to IFN-alpha therapy. To elucidate the mechanism involved in the therapeutic effect of IFN-alpha, we have analyzed the pattern of phosphorylated proteins in hairy cells. We detected the presence of a hyperphosphorylated protein with a molecular mass of about 35 kDa. This protein was identified as the CD20 molecule (B1), which is a structurally unique phosphoprotein exclusively detected on B cells and expressed during most stages of B cell development. Incubation of hairy cells with mitogenic concentrations of LMW-BCGF induces an additional increase in CD20 protein phosphorylation. In contrast, preincubation of cells with IFN-alpha, but not IFN-gamma, decreases both basal and LMW-BCGF-induced CD20 phosphorylation. CD20 phosphorylation in hairy cells is also reduced after in vivo IFN-alpha administration. In contrast, in one case of a patient unresponsive to IFN-alpha therapy, CD20 phosphorylation is not altered by in vitro IFN-alpha treatment, whereas LMW-BCGF still elicits CD20 phosphorylation stimulation. Our results suggest that IFN-alpha may act in HCL, at least in part, by inhibiting leukemic cell proliferation via regulation of phosphorylation, since CD20 phosphorylation is thought to be associated with cellular proliferation. A model involving dysregulation of CD20 is discussed.


Causes and characteristics of death in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: a retrospective cohort study.
Acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are associated with high in-hospital mortality. However, in cohorts of ARDS patients from the 1990s, patients more commonly died from sepsis or multi-organ failure rather than refractory hypoxemia. Given increased attention to lung-protective ventilation and sepsis treatment in the past 25 years, we hypothesized that causes of death may be different among contemporary cohorts. These differences may provide clinicians with insight into targets for future therapeutic interventions. We identified adult patients hospitalized at a single tertiary care center (2016-2017) with AHRF, defined as PaO2/FiO2 ≤ 300 while receiving invasive mechanical ventilation for > 12 h, who died during hospitalization. ARDS was adjudicated by multiple physicians using the Berlin definition. Separate abstractors blinded to ARDS status collected data on organ dysfunction and withdrawal of life support using a standardized tool. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. We identified 385 decedents with AHRF, of whom 127 (33%) had ARDS. The most common primary causes of death were sepsis (26%), pulmonary dysfunction (22%), and neurologic dysfunction (19%). Multi-organ failure was present in 70% at time of death, most commonly due to sepsis (50% of all patients), and 70% were on significant respiratory support at the time of death. Only 2% of patients had insupportable oxygenation or ventilation. Eighty-five percent died following withdrawal of life support. Patients with ARDS more often had pulmonary dysfunction as the primary cause of death (28% vs 19%; p = 0.04) and were also more likely to die while requiring significant respiratory support (82% vs 64%; p < 0.01). In this contemporary cohort of patients with AHRF, the most common primary causes of death were sepsis and pulmonary dysfunction, but few patients had insupportable oxygenation or ventilation. The vast majority of deaths occurred after withdrawal of life support. ARDS patients were more likely to have pulmonary dysfunction as the primary cause of death and die while requiring significant respiratory support compared to patients without ARDS.


Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes.
The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800-3600 cm(-1). Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R⋅H⋅3](+), showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R⋅H⋅3](+) complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen-bonding interactions between the C(2')-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host.


Different types of "dissociation" have different psychological mechanisms.
The term "dissociation" has been used to describe a wide range of psychological and psychiatric phenomena. The popular conception of dissociation describes it as a unitary phenomenon, with only quantitative differences in severity between the various dissociative conditions. More recently, it has been argued that the available evidence is more consistent with a model that identifies at least two distinct categories of dissociative phenomena-"detachment" and "compartmentalization"- that have different definitions, mechanisms and treatment implications (Holmes, Brown, Mansell, Fearon, Hunter, Frasquilho & Oakley 2005). This paper presents evidence for this bipartite model of dissociation, followed by definitions and descriptions of detachment and compartmentalization. Possible psychological mechanisms underlying these phenomena are then discussed, with particular emphasis on the nature of compartmentalization in conversion disorder, hypnosis, dissociative amnesia and dissociative identity disorder.


Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis.
Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.


The Epistemic Injustice of Racial Injustice.
The treatment of essential health care providers belonging to racial and ethnic minority groups is a bioethical issue. Minority providers hold valuable knowledge of the racism they experience. However, they are continuously doubted, discredited, and disempowered as epistemic interlocutors. Such epistemic injustice has ethical repercussions for the treatment of patients. The unwillingness of colleagues to receive the authors' experiential knowledge of racism, their testimonies on its impacts, and their efforts to correct inaccurate judgments amount to a morally problematic epistemological stance. Additional moral considerations include the lack of guidance on dealing with racism in health care institutions, the marginalization of minority providers, an inflexible medical culture, the need for anti-racist frameworks, and the unique vulnerability of students and trainees. These narratives call for a sustained effort in balancing the pursuit of individual virtues and the creation of systemic conditions necessary to eliminate racial injustice.


Bracken-fern extracts induce cell cycle arrest and apoptosis in certain cancer cell lines.
Bracken fern [Pteridium aquilinem (L.) kuhn (Dennstaedtiaceae)] is one of the most common species on the planet. It has been consumed by humans and animals for centuries. Use by some human groups is because they believe bracken fern is good for health as plant medicine. However, it is also one of the few known plants that can cause tumors in farm animals. Many interested groups have focused their attention on bracken fern because of these interesting features. In order to evaluate the biological effects of exposure to this plant in cellular level, human cancer cell lines were treated with the fern dichloromethane extracts and the genotoxic and cytotoxic effects were studied. Anti-proliferative/cytotoxic effects were evaluated by cell count, MTT assay and flow cytometry methods with three different cancer cell lines, TCC, NTERA2, and MCF-7, and two normal cells, HDF1 and HFF3. Pro-apoptotic effects of the extracts were determined by DAPI staining and comet assay, on TCC cancer cells compared to the normal control cell lines. Cellular morphology was examined by light microscopy. Our present study showed that the extract caused DNA damage and apoptosis at high concentrations (200 μg/mL) and also it may induce cell cycle arrest (G2/M phase) at mild concentrations (50 and 30 μg/mL) depending on the cell type and tumor origin. These results indicate that bracken fern extract is a potent source of anticancer compounds that could be utilized pharmaceutically.


[Vertebroplasty: state of the art].
Over the last 10 years, there has been much development in the management of metastatic and osteoporotic vertebral compression fractures using vertebroplasty. This percutaneous image-guided interventional radiology procedure allows stabilization of a vertebral body by injection of an acrylic cement and frequently results in significant symptomatic relief. During cement polymerisation, an exothermic reaction may destroy adjacent tumor cells. Advances have been made to reduce complications from extravasation of cement in veins or surrounding soft tissues. Safety relates to experience but also to technical parameters: optimal cement radio-density, adequate digital fluoroscopy unit (single or bi-plane digital angiography unit), development of cements other than PMMA to avoid the risk of adjacent vertebral compression fractures. The rate of symptomatic relief from vertebroplasty performed for its principal indications (vertebral hemangioma, metastases, osteoporotic fractures) reaches 90-95%. The rate of complications is about 2% for metastases and less than 0.5% for osteoporotic fractures. Vertebroplasty plays a major role in the management of specific bone weakening vertebral lesions causing, obviating the need for kyphoplasty.


Regulation of THI4 (MOL1), a thiamine-biosynthetic gene of Saccharomyces cerevisiae.
THI4, a Saccharomyces cerevisiae gene originally identified as a result of transient expression in molasses medium and named MOL1 is regulated by thiamine. Using a THI4 promoter-lacZ fusion on a centromeric yeast vector, we have shown that the THI4 is completely repressed throughout batch culture by thiamine at a concentration around 1 microM, but shows high level constitutive expression in thiamine-free medium. The transient expression pattern observed in molasses medium can be mimicked by the addition of 0.15 microM-thiamine to defined minimal medium. Cells grown in thiamine-free medium have an intracellular thiamine concentration of around 9 pmol/10(7) cells. A low level (1 microM) of exogenous thiamine is completely sequestered from the medium within 30 min; intracellular thiamine concentrations rise rapidly, followed by a gradual decrease as a result of dilution during growth. A saturating extracellular level of thiamine leads to a maximal intracellular concentration of around 1600 pmol/10(7) cells, at which point the transport system is shut down. After transfer from repressing to non-repressing medium, THI4 becomes induced when the intracellular concentration of thiamine falls to 20 pmol/10(7) cells. A thi4::URA3 disruption strain is auxotrophic for thiamine, but can grow in the presence of hydroxyethyl thiazole, indicating that the gene product is involved in the biosynthetic pathway leading to the formation of the thiazole precursor of thiamine.


The phase diagrams of KCaF3 and NaMgF3 by ab initio simulations.
ABF3 compounds have been found to make valuable low-pressure analogues for high-pressure silicate phases that are present in the Earth's deep interior and that may also occur in the interiors of exoplanets. The phase diagrams of two of these materials, KCaF3 and NaMgF3, have been investigated in detail by static ab initio computer simulations based on density functional theory. Six ABF3 polymorphs were considered, as follows: the orthorhombic perovskite structure (GdFeO3-type; space group Pbnm); the orthorhombic CaIrO3 structure (Cmcm; commonly referred to as the "post-perovskite" structure); the orthorhombic Sb2S3 and La2S3 structures (both Pmcn); the hexagonal structure previously suggested in computer simulations of NaMgF3 (P63/mmc); the monoclinic structure found to be intermediate between the perovskite and CaIrO3 structures in CaRhO3 (P21/m). Volumetric and axial equations of state of all phases considered are presented. For KCaF3, as expected, the perovskite phase is shown to be the most thermodynamically stable at atmospheric pressure. With increasing pressure, the relative stability of the KCaF3 phases then follows the sequence: perovskite → La2S3 structure → Sb2S3 structure → P63/mmc structure; the CaIrO3 structure is never the most stable form. Above about 2.6 GPa, however, none of the KCaF3 polymorphs are stable with respect to dissociation into KF and CaF2. The possibility that high-pressure KCaF3 polymorphs might exist metastably at 300 K, or might be stabilised by chemical substitution so as to occur within the standard operating range of a multi-anvil press, is briefly discussed. For NaMgF3, the transitions to the high-pressure phases occur at pressures outside the normal range of a multi-anvil press. Two different sequences of transitions had previously been suggested from computer simulations. With increasing pressure, we find that the relative stability of the NaMgF3 phases follows the sequence: perovskite → CaIrO3 structure → Sb2S3 structure → P63/mmc structure. However, only the perovskite and CaIrO3 structures are stable with respect to dissociation into NaF and MgF2.


Transcription of immune related genes in Solea senegalensis vaccinated against Photobacterium damselae subsp. piscicida. Identification of surrogates of protection.
Solea senegalensis is a flatfish with a great potential for aquaculture, but infectious diseases restrict its production, being this fish species highly susceptible to Photobacterium damselae subsp. piscicida (Phdp) infections. A better understanding of the mechanisms related to fish immune response is crucial for the development of effective approaches in disease management. In the present work, transcriptional changes of immune related genes have been evaluated in farmed S. senegalensis specimens vaccinated against Phdp by intraperitoneal injection (IP) and immersion (IM). IP fish showed higher antibody levels and increased transcription of genes encoding lysozyme C1, complement factors involved in the classical pathway and components involved in the opsonization and the limitation of free iron availability, all of them facilitating the faster elimination of the pathogen and promoting higher RPS after the infection with Phdp. The results of this study seem to support a different intensity of the specimens immune response in the head kidney. Analysis of the immune response in 15 day post-challenged fish showed up-regulation of genes involved in all stages of S. senegalensis immune response, but especially those genes encoding proteins related to the innate response such as complement, lysozyme and iron homeostasis in the head kidney. On the other hand, liver transcription was higher for genes related to inflammation, apoptosis and cell mediated cytotoxicity (CMC). Furthermore, comparison of the differential response of S. senegalensis genes in vaccinated and unvaccinated fish to Phdp infection allowed the identification of a potential biosignature, consisting in 10 genes, as a surrogate of protection and therefore, as indicator of vaccine success against fotobacteriosis after IP vaccination. These results provide important insights into the S. senegalensis protection against Phdp induced by vaccination.


C-reactive protein: clinical applications and proposals for a rational use.
C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards, and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.


The Total Artificial Heart in End-Stage Congenital Heart Disease.
The development of durable ventricular assist devices (VADs) has improved mortality rates and quality of life in patients with end stage heart failure. While the use of VADs has increased dramatically in recent years, there is limited experience with VAD implantation in patients with complex congenital heart disease (CHD), despite the fact that the number of patients with end stage CHD has grown due to improvements in surgical and medical care. VAD use has been limited in patients with CHD and end stage heart failure due to anatomic (systemic right ventricle, single ventricle, surgically altered anatomy, valve dysfunction, etc.) and physiologic constraints (diastolic dysfunction). The total artificial heart (TAH), which has right and left sided pumps that can be arranged in a variety of orientations, can accommodate the anatomic variation present in CHD patients. This review provides an overview of the potential use of the TAH in patients with CHD.


Transvenous catheter cryoablation of the atrioventricular node and visual assessment of freezing of cardiac tissue using intracardiac echocardiography.
We investigated the use of a catheter-based cryoablation system on atrioventricular (AV) junction ablation in dogs. In five dogs, the cryoablation catheter was introduced to the AV junction area in order to create transient high degree or complete AV block. Cryo-freezing energy was applied by lowering the temperature to -75 degrees C for five minutes as a single cycle. This cycle was repeated until significant impairment of the AV conduction appeared. Transient high degree and complete AV block was obtained in all five dogs without any adverse effects. The iceball formation was identified by intracardiac echocardiography. Ablation of the AV junction is effective with several freeze-thaw cycles using a transvenous catheter cryoablation system.


Family Medicine Education with Virtual Patients: a Qualitative Study.
Virtual patients (VP) have been present within the medical education process for some time. Although they are assumed to be of great benefit for student learning, very little is know about student perception and outcomes of learning, especially during the pre-clerkship years. Therefore we have decided to investigate the use of VPs during lectures, which has never been analyzed before, but could present an opportunity for more effective and holistic learning. This was a qualitative study among the 4th year undergraduate medical students at the Medical Faculty, University of Maribor, Slovenia. Students, after completing 4 virtual patient cases during the semester, were asked to participate in focus groups. Using these focus groups we asked students to provide information about their perceptions of VP cases, their learning, and suggestions for educational improvements. Data was transcribed and analyzed using the grounded theory-based coding method (open coding). Medical students reported having a positive attitude towards virtual patient learning. They perceived them as helpful for filling in knowledge gaps, learning appropriate patient care and clinical reasoning. However, especially within the setting of early clinical learning, students felt the need to discuss their questions with their tutors in order to achieve better learning outcomes. Students on teaching courses feel the need for structured instructor sessions and the integration of VPs in the course planning in order to maximize their learning outcomes.


The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer.
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer.


[Anterior lumbar intercorporal spondylodesis. Radiological and functional therapeutic results].
The purpose of this investigation was to identify risk factors in relation to non-union following lumbar intercorporal spondylodesis and to correlate this result with the functional outcome as assessed by the Dallas Pain Questionnaire (DPQ). This comprises questions concerning daily activities, work-leisure activities, anxiety-depression and social interest, measured on visual analog scales. During the period 1979-87 a total of 132 patients were operated with spondylodesis, diagnosed as suffering from spondylolisthesis or disc degeneration. Minimal follow-up was one year. Radiological graft incorporation was complete in 52% of the cases, partial in 24% and lacking in 24%. The rate of functional outcome follow-up was 72%. Seventy percent claimed an improvement in three out of four categories. Thirty percent claimed no improvement or worsened condition. The DPQ showed signs of poor prognosis for age groups above 45 (p < 0.04) and those with former spine surgery (p < 0.02). The questionnaire showed significantly better results for the group with perfect or doubtful union compared to the group with non-union (p < 0.006). In conclusion this investigation demonstrates a success rate of 70% for anterior lumbar interbody fusion. There is a tendency to poorer prognosis for patients with previous spine surgery and age above 45 years. The Dallas Pain Questionnaire correlates significantly to X-ray analysis and seems to be a useful tool for the description of individual biopsychosocial changes following spine surgery.


Pulsed-field electrophoretic fingerprinting of Salmonella indiana and its epidemiological applicability.
Eight Xba I-generated pulsed-field profile (PFP) types and four subtypes within one of the most common PFP types have been identified in Salmonella indiana from patients, poultry and human food in England and Wales in the three-year period from January 1994 to December 1996. Two PFP types have predominated, PFP X1 and PFP X2. Although the PFP X1 type was identified throughout the study period, the PFP X2 type was not identified until late 1995, subsequently becoming the most common PFP type in humans in the first six months of 1996 with a significant distribution in elderly patients. It is concluded that PFGE can be used in support of epidemiological investigations for the subdivision of Salm. indiana. Furthermore, as both conditions and interpretation criteria can be easily standardized, it is suggested that for many salmonella serotypes, PFGE can provide the basis for a definitive scheme of genotypic subtyping suitable for epidemiological investigations at both a national and international level.


Performance of residents using digital images versus glass slides on certification examination in anatomical pathology: a mixed methods pilot study.
It is anticipated that many licensing examination centres for pathology will begin fully digitizing the certification examinations. The objective of our study was to test the feasibility of a fully digital examination and to assess the needs, concerns and expectations of pathology residents in moving from a glass slide-based examination to a fully digital examination. We conducted a mixed methods study that compared, after randomization, the performance of senior residents (postgraduate years 4 and 5) in 7 accredited anatomical pathology training programs across Canada on a pathology examination using either glass slides or digital whole-slide scanned images of the slides. The pilot examination was followed by a post-test survey. In addition, pathology residents from all levels of training were invited to participate in an online survey. A total of 100 residents participated in the pilot examination; 49 were given glass slides instead of digital images. We found no significant difference in examination results between the 2 groups of residents (estimated marginal mean 8.23/12, 95% confidence interval [CI] 7.72-8.87, for glass slides; 7.84/12, 95% CI 7.28-8.41, for digital slides). In the post-test survey, most of the respondents expressed concerns with the digital examination, including slowly functioning software, blurring and poor detail of images, particularly nuclear features. All of the respondents of the general survey (n = 179) agreed that additional training was required if the examination were to become fully digital. Although the performance of residents completing pathology examinations with glass slides was comparable to that of residents using digital images, our study showed that residents were not comfortable with the digital technology, especially given their current level of exposure to it. Additional training may be needed before implementing a fully digital examination, with consideration for a gradual transition.


[Not Available].
The military and revolutionary activity of Bulgarian physicians (enlighteners) during the Turkish yoke is closely connected with the wars of Russia waged against Turkey. The Bulgarian physicians were active in the military and revolutionary field also during the Serbian-Turkish war in 1876. About 20 Bulgarian physicians and pharmacologists were included in the composition of the Russian sanitary missions and in those of the Roumanians. The participation in the above wars enabled the Bulgarian physicians to get acquainted as early as before the liberation, with the problems of military medicine--an experience which proved very helpful in the establishment of the first Bulgarian field medical service during the Liberation war.


The Antecedents of Thriving at Work: A Meta-Analytic Review.
In this study, a systematic and comprehensive meta-analysis of the relationship between thriving at work and its antecedents is conducted. The antecedents in terms of the characteristics of unit contextual features, the resources produced at work, agentic work behaviors, and personality traits are illustrated according to the socially embedded model of thriving described by Spreitzer and research. Additionally, we examine possible cultural influence on the relationship between thriving and its antecedents at different levels of individualistic culture. According to 67 independent samples (N = 28,097), our findings reveal the correlations between thriving at work and the antecedents such as those in the form of unit contextual features, the resources produced at work, agentic work behaviors, and personality traits. Furthermore, we find that individualism moderate the relationships between certain antecedents and thriving at work. Finally, we discuss the theoretical and practical implications of this study as well as the directions for future research.


Species and tissue differences of histamine storage and release.
Histamine release by compound 48/80 was studied in vivo and in vitro in different tissues of the cat and rat. A good correlation was fond between both kinds of experiment. The histamine stores in the cat salivary gland are poorly sensitive to this histamine-liberating substance. In vitro studies with heart and lungs of the rat and guinea pig showed no correlation between the spontaneous histamine release and the release induced by compound 48/80. This finding suggests the existence of two pools of tissue histamine, both with different storage and release properties, and most probably with different functions in the body.


[The value and limits of endorectal sonography in the preoperative stage classification of rectal cancer].
The article deals with the valuation of endorectal and abdominal sonography in preoperative staging of rectal carcinoma. Data processing of 40 patients suffering from tumours of the rectum examined rectoscopically, by biopsy and via sonography showed that endorectal sonography can achieve preoperative staging (T) with a sensitivity of 89%, a specificity of 100%, a positive predictive value of 89% and a negative predictive value of 100%, the overall accuracy being 81%. Identification of pararectal adenopathies can be performed with a sensitivity of 16% and a specificity of 100%. Liver metastases were determined with a sensitivity and specificity of 100%. Hence, endorectal sonography is a valuable method for preoperative staging of carcinoma of the rectum.


A Highly Selective and Sensitive Colorimetric Probe for Cu2+ Determination in Aqueous Media Based on Derivative of Tryptanthrin.
A new colorimetric probe, based on tryptanthrin derivative (TR-A), has been successfully synthesized. The probe shows good selectivity and sensitivity for Cu2+ over 12 competing metal ions in a 10 mM Tris-HCl buffer solution (pH 5.5). A significant peak at 623nm appears in the UV-Vis absorption of TR-A-Cu2+, and a noteworthy color change is observed with the naked eye from aquamarine blue to light orange. The interaction of TR-A and Cu2+ are proven to form a 1:1 binding stoichiometry; this identifying is expected to be completed within 1 min. The probe with a limit of detection (16 nM, R2 = 0.9934) shows excellent potential to determine Cu2+ in analysis systems.


Occupational risks for primary liver cancer in Shanghai, China.
Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis.


The Soybean Basic Helix-Loop-Helix Transcription Factor ORG3-Like Enhances Cadmium Tolerance via Increased Iron and Reduced Cadmium Uptake and Transport from Roots to Shoots.
Cadmium (Cd) is one of the most dangerous heavy metal pollutants in the environment and is toxic to animal and plant cells. On the other hand, iron (Fe) is an essential element for plant growth and development. The chlorosis of plant leaves under cadmium stress is similar to the typical symptom of iron deficiency. Recently, several Arabidopsis basic/helix-loop-helix (bHLH) transcription factors have been identified that are involved in the interactions between Cd and Fe. In the present study, over-expression the ORG3-like gene GmORG3, a bHLH transcription factor OBP3-responsive gene (ORG), enhanced Cd tolerance and stabilized Fe homeostasis. The domain analysis of GmORG3 showed that the protein contains a conserved 61-residue bHLH domain belonging to subfamily II. Moreover, subcellular localization experiments showed that GmORG3 is a nucleoprotein. GmORG3 was transcribed only in soybean roots and was significantly induced by external Cd stress in soybean plants. Heterologous expression of GmORG3 enhanced Cd tolerance in yeast. Furthermore, the overexpression of GmORG3 in soybean mosaic seedlings using a hairy root system showed that overexpressing plants increased the translocation ratio of Fe but reduced Cd translocation from the roots to shoots. In addition, the ectopic expression of GmORG3 in tobacco reduced phytotoxic effects induced by Cd stress and Fe deficiency, including the blockage of root elongation and decreased chlorophyll content. By integrating all these results, we found that GmORG3 plays an important role in response to Cd stress. The results provide new insights into the molecular mechanisms of Cd tolerance in soybean.


Evaluation and Comparison of Antibacterial Efficacy of Herbal Extracts in Combination with Antibiotics on Periodontal pathobionts: An in vitro Microbiological Study.
In the past few decades focus of research has been toward herbal medicines because of growing bacterial resistance and side effects of antimicrobial agents. The extract derived from the plants may increase the efficacy of antibiotics when used in combination against pathogenic bacteria. In the current study, the synergistic antibacterial efficacy of plant extracts in combination with antibiotics has been assessed on selected periodontal pathogens. Ethanolic extracts were prepared from Salvadora persica (Miswak) and Cinnamomum zeylanicum (Ceylon cinnamon), by the soxhalate method. Plaque samples were collected from clinical periodontitis patients to isolate and grow the periodontal pathobionts under favorable conditions. Susceptibility of bacteria to the extracts was assessed by gauging the diameter of the inhibition zones. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of plant extracts were determined against each bacterium. Synergistic activity of plants extract in combination with antibiotics against the bacteria was also assessed by measuring the diameter of the inhibition zones. Ethanolic extract of both the plants showed an inhibitory effect on the proliferation and growth of all four strains of periodontal pathobionts. Maximum antibacterial activity was exhibited by C. zeylanicum against Tannerella forsythia (MIC = 1.56 ± 0.24 mg/mL, MBC = 6.25 ± 0.68 mg/mL), whereas among all the studied groups the minimum activity was reported by C. zeylanicum against Aggregatibacter actinomycetemcomitans the (MIC = 12.5 ± 3.25 mg/mL, MBC = 75 ± 8.23 mg/mL). Combination of herbal extracts with different antibiotics revealed a synergistic antibacterial effect. The best synergism was exhibited by S. persica with metronidazole against A. actinomycetemcomitans (27 ± 1.78). Current in vitro study showed variable antibacterial activity by experimented herbal extracts against periodontal pathobionts. The synergistic test showed significant antibacterial activity when plant extracts were combined with antibiotics.


Methods of collection and lipid composition of teat canal keratin in dry and lactating cows.
Methods for collecting keratin from the teat canal were examined to select a procedure to obtain representative samples for lipid analysis. Data obtained by solvent extraction of excised teats were compared with those obtained by scraping keratin from dissected teats of lactating and dry cows. Solvent extraction with petroleum ether or 2:1 chloroform-methanol yielded similar dry weights of material. However, both solvents removed large amounts of material other than keratin from the teat canal. The lipid class and fatty acid profiles of the material extracted by solvent flushing were not similar to profiles obtained by scraping keratin from the teat canal. A metal tapestry needle was suitable for collection of keratin from the teat canal of living cows. About 78% of the keratin present in the teat was collected with the needle. Lipid composition of keratin collected with the needle was the same as in keratin scraped from excised teats. The tapestry needle was suitable as a tool for collecting repeatable, representative samples of keratin for analysis from single teat canals of living cows.


[Epidemiological trend of early-onset gastric cancer and late-onset gastric cancer in China from 2000 to 2019].
Objective: In order to understand the changing trends of gastric cancer incidence and mortality in early-onset and late-onset in China from 2000 to 2019. Methods: The Global Burden of Disease research data was collected, and Excel and R 4.2.1 softwares were used to examine the incidence rate, mortality rate, and disability-adjusted life years (DALY) of Chinese people from 2000 to 2019, with a focus on gender, age, and year. Results: In 2019, the crude incidence rates were 7.06/100 000 (95%UI: 6.63/100 000-7.59/100 000) and 114.52/100 000 (95%UI: 108.79/100 000-121.63/100 000) for early- and late-onset gastric cancer, respectively. The crude mortality rate for early-onset gastric cancer was 3.29/100 000 (95%UI: 3.11/100 000- 3.50/100 000), while the crude mortality rate for late-onset gastric cancer was 81.88/100 000 (95%UI: 78.15/100 000-86.04/100 000). Additionally, the crude DALY rates for these two types of gastric cancer were 156.48/100 000 (95%UI: 148.82/100 000-165.84/100 000) and 1 750.13/100 000 (95%UI: 1 661.21/100 000-1 852.99/100 000). The standardized incidence of early-onset gastric cancer decreased from 5.49/100 000 in 2000 to 4.76/100 000 in 2019, and that of late-onset gastric cancer decreased from 143.45/100 000 in 2000 to 123.02/100 000 in 2019.The standardized mortality rate of early-onset gastric cancer decreased from 4.16/100 000 in 2000 to 2.18/100 000 in 2019, and that of late-onset gastric cancer decreased from 140.82/100 000 in 2000 to 91.49/100 000 in 2019. The standardized DALY rate for early-onset gastric cancer in 2019 was 105.87/100 000 (95%UI: 87.98/100 000 -125.60/100 000), lower than 198.84/100 000 (95%UI: 179.47/100 000- 219.83/100 000) in 2000. The standardized DALY rate for late onset gastric cancer in 2019 was 1 821.11/100 000 (95%UI: 1 509.42/100 000-2 158.53/100 000), lower than 2 932.52/100 000 (95%UI: 2 665.92/100 000-3 252.60/100 000) in 2000. Conclusions: The standardized mortality rate of early-onset gastric cancer in China showed a decreasing trend from 2000 to 2019. The standardized mortality rate of late onset gastric cancer showed a trend of first increasing and then decreasing. Notably, the incidence, mortality, and DALY of late-onset gastric cancer were significantly higher than those of early-onset gastric cancer during this period. Additionally, male incidence, mortality, and crude DALY rates were higher than female.


[Mitochondrial 12S rRNA variants studies in 456 subjects with hearing loss in seven schools for deaf and mutes in Zhejiang province].
To investigate mutational spectrum and frequency of the mitochondrial 12S rRNA gene in Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss. Total of 456 subjects with non-syndromic hearing loss were recruited from seven schools for deaf-mutes in Zhejiang province. Genomic DNA was extracted from the whole blood, and then the DNA fragment was amplified spanning the 12S rRNA gene, followed by sequencing and analyzed. Thirty-one variants were identified by mutation analysis of 12S rRNA gene in these subjects. The frequency of the known 1555A > G mutation was 4.4% (20/456). Prevalence of other putative deafness-associated mutation at positions 961 and 1095 were 2.0% (9/456) and 0.7% (3/456) respectively. Furthermore, the 1027A > G, 1109T > C and 1431G > A variants conferred increased sensitivity to ototoxic drugs or non-syndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this 12S rRNA gene. Moreover, clinical data showed a wide range of age-of-onset, variety of severity and various audiometric configurations in subjects carrying the 1555A > G mutation. Our data demonstrated that the mitochondrial 12S rRNA gene is the hot spot for mutations associated with aminoglycoside ototoxicity and non-syndromic hearing loss. Nuclear modifier genes, mitochondrial haplotypes and environmental factors might play a role in the phenotypic manifestation of these mutations.


Breast specimen handling and reporting in the post-neoadjuvant setting: challenges and advances.
Neoadjuvant systemic therapy is becoming more commonly used in patients with earlier stages of breast cancer. To assess tumour response to neoadjuvant chemotherapy, pathological evaluation is the gold standard. Depending on the treatment response, the pathological examination of these specimens can be quite challenging. However, a uniform approach to evaluate post-neoadjuvant-treated breast specimens has been lacking. Furthermore, there is no single universally accepted or endorsed classification system for assessing treatment response in this setting. Recent initiatives have attempted to create a standardised protocol for evaluation of post-neoadjuvant breast specimens. This review outlines the necessary information that should be collected prior to macroscopic examination of these specimens, the recommended and most pragmatic approach to tissue sampling for microscopic examination, describes the macroscopic and microscopic features of post-therapy breast specimens, summarises two commonly used systems for classifying treatment response and outlines the critical variables that should be included in the final pathology report.


[Action on the isolated guinea-pig ileum and toxicity of some derivatives of 1,5-bis-(3,4-methylendioxyphenyl)-n. pentane].
The acute toxicity and the activity on isolated guinea pig ileum of some derivatives of 1,5-bis-(3,4-methylendioxyphenyl)-n.pentane are reported. The majority of such compounds showed clear antagonist activity towards BaCl2, acetylcholine, histamine and 5-HT contracting responses, generally greater than that of papaverine. In almost all cases the therapeutic index of these compounds, calculated as the ratio between mouse i.v. LD50 and ileum ED50, was greater than the therapeutic index of papaverine.


Visualization of RecA filaments and DNA by fluorescence microscopy.
We have developed two experimental methods for observing Escherichia coli RecA-DNA filament under a fluorescence microscope. First, RecA-DNA filaments were visualized by immunofluorescence staining with anti-RecA monoclonal antibody. Although the detailed filament structures below submicron scale were unable to be measured accurately due to optical resolution limit, this method has an advantage to analyse a large number of RecA-DNA filaments in a single experiment. Thus, it provides a reliable statistical distribution of the filament morphology. Moreover, not only RecA filament, but also naked DNA region was visualized separately in combination with immunofluorescence staining using anti-DNA monoclonal antibody. Second, by using cysteine derivative RecA protein, RecA-DNA filament was directly labelled by fluorescent reagent, and was able to observe directly under a fluorescence microscope with its enzymatic activity maintained. We showed that the RecA-DNA filament disassembled in the direction from 5' to 3' of ssDNA as dATP hydrolysis proceeded.


Gender, personal networks, and drug use among rural African Americans.
One of the main unifying concepts of research examining gender variations in drug use behavior is the social network. Yet, research specifically focusing on how the social networks of these groups differ by gender is limited. Few studies have investigated the social networks of rural African Americans who use drugs. In this study, we compared the personal networks of 20 rural African-American men and women addicted to cocaine using social network analysis (SNA) methods. The data do not support strong assertions about gender differences in the personal networks of the study sample. However, the results of the study suggest that men tend to have more drug users in their networks than women, as well as less structurally cohesive networks. Women tend to include more men in their personal networks than men included women. Implications of the research results for network-based drug prevention intervention as well as the value of SNA methods for drug use research are discussed.


Grading of Diffuse Astrocytic Gliomas: A Review of Studies Before and After the Advent of IDH Testing.
Estimating the malignancy level of tumors is key to management, and has been part of oncology practice for the past ∼100 years. A central aspect of assessing malignancy level is based on histological "grading"-a process in which a pathologist evaluates microscopic features of a tumor and interprets those findings in light of large prognostic studies. For the diffuse astrocytic gliomas, there have been many such studies over the past century and these have proven useful in estimating prognosis for patients. With the advent of molecular genetics, molecular diagnostic testing has been added to histological evaluation in the armamentarium of the pathologist, and the recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System encourages testing for isocitrate dehydrogenase (IDH) gene status in the classification of diffuse astrocytic gliomas. The present review catalogues a large series of diffuse astrocytic glioma grading studies over the past few decades, and compares the prognostic value of such grading schema before and after the emergence of IDH testing. The review concludes that novel approaches to diffuse astrocytic tumor grading are required in the era of IDH testing.


Different effects of methylphenidate and atomoxetine on the behavior and brain transcriptome of zebrafish.
Attention deficit-hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder found in children. It is characterized by inattention, hyperactivity, and impulsivity. Methylphenidate (MPH) and atomoxetine (ATX) are commonly prescribed for the treatment of ADHD. In the present study, we examined the behavioral and brain transcriptome changes in MPH-treated and ATX-treated zebrafish. In behavioral analysis, zebrafish showed opposite response to each treatment. MPH-treated fish showed higher anxiety-like behavior while ATX-treated fish showed lower anxiety-like behavior. Further, we performed RNA sequencing analysis of zebrafish brain to elucidate the underlying biological pathways associated with MPH and ATX treatment. Interestingly, we found that shared differentially expressed genes in MPH-treated and ATX-treated fish were instrumental in cholesterol biosynthesis pathway and were regulated in opposite manner. Our findings highlight the contrast between MTH and ATX, and may suggest the alterations in clinical practice for these medications and drug development for ADHD.


Myoglobin oxidation in a model system as affected by nonheme iron and iron chelating agents.
A model system was used to study the effect of nonheme iron on myoglobin oxidation at pH 5.6 and pH 7.2 at 23 degrees C. The addition of ferrous iron significantly (p < 0.05) increased the rate of myoglobin oxidation in the absence of lipid, demonstrating that iron promoted myoglobin oxidation independent of the effect of lipid oxidation. The addition of the type II, iron chelating antioxidants sodium tripolyphosphate (at pH 7.2) or milk mineral (at pH 5.6) negated the effect of added iron, slowing oxidation of myoglobin. A clear concentration dependence was seen for iron-stimulated myoglobin oxidation, based on both spectral and visual evidence. Further investigation is needed to determine the possible role for nonheme ferrous iron on myoglobin oxidation in vivo or in meat.


Postsurgical Stability of Temporomandibular Joint of Skeletal Class III Patients Treated with 2-Jaw Orthognathic Surgery via Computer-Aided Three-Dimensional Simulation and Navigation in Orthognathic Surgery (CASNOS).
The aim of this study is to clarify the postsurgical stability of temporomandibular joints in skeletal class III patients treated with 2-jaw orthognathic surgery which was performed utilizing computer-aided three-dimensional simulation and navigation in orthognathic surgery (CASNOS) protocol. 23 consecutive nongrowing skeletal class III patients with mandibular prognathism associated with maxillary retrognathism treated with 2-jaw orthognathic surgery between 2018 and 2019 were enrolled in this study. The surgery was planned according to the standardized protocol of CASNOS (computer-aided three-dimensional simulation and navigation in orthognathic surgery). Computed tomography (CT) scans were performed in all patients 3 weeks presurgically and 6 months postsurgically. ITKSNAP and 3D Slicer software were used to reconstruct three-dimensional facial skeletal images, to carry out image segmentation, and to superimpose and quantify the TMJ position changes before and after surgery. Amount of displacement of the most medial and lateral points of the condyles and the change of intercondylar angles were measured to evaluate the postsurgical stability of TMJ. A total amount of 23 skeletal class III patients (female : male = 12 : 11) with age ranged from 20.3 to 33.5 years (mean: 24.39 ± 4.8 years old) underwent Le Fort I maxillary advancement and BSSO setback of the mandible. The surgical outcome revealed the satisfactory correction of their skeletal deformities. The mean displacement of the right most lateral condylar point (RL-RL') was 1.04 ± 0.42 mm and the mean displacement of the left most lateral condylar point (LL-LL') was 1.19 ± 0.41 mm. The mean displacement of the right most medial condylar point (RM-RM') was 1.03 ± 0.39 mm and the left most medial condylar point (LM-LM') was 0.96 ± 0.39 mm. The mean intercondylar angle was 161.61 ± 5.08° presurgically and 159.28 ± 4.92° postsurgically. The postsurgical position of TM joint condyles in our study only presented a mild change with all the landmark displacement within a range of 1.2 mm. This indicates the bimaxillary orthognathic surgery via 3D CASNOS protocol can achieve a desired and stable result of TMJ position in treating skeletal class III adult patients with retrognathic maxilla and prognathic mandible.


Coxsackievirus B5 infections in acute oliguric renal failure.
Six patients with acute oliguric renal failure were studied for detection of acute viral or mycoplasma infection. Precipitating causes, such as streptococcal infection, use of nephrotoxic drugs, etc., were ruled out. Tests for neurtralization and complement fixation antibodies, in which 19 viral and mycoplasma agents were used as antigens, demonstrated a recent coxsachievirus B5 infection in five of six patients. Rises in titer to other antigens tested were not noted. A group of control patients showed no significant rises in titer of antibody to coxsackievirus B5. These studies strongly suggest that an association exists between coxsackievirus B5 infections and acute oliguric renal failure. Whether this association is etiologic is not known.


Thoracic injury: a review of 276 cases.
Chest injury, one of the most important aspects of trauma, directly accounts for 25% of all trauma-related deaths and plays a major contributing role in another 25% of trauma deaths. This paper aimed to explore the spectrum and outcome of thoracic injuries seen in a multi centric study of trauma patients. A total of 276 consecutive trauma patients in 6 general hospitals were analyzed. The feature of injury, injury severity score (ISS), clinical treatment and mortality were recorded in a prospective manner and analyzed retrospectively. Multiple logistic regression analysis was used to determine the independent predictors of mortality following the chest trauma. There were 246 males (89.1%) and 30 females (10.9%) ranging from 3 to 80 years with a mean age of (34+/-17) years. Road traffic accident was the main cause of injury, especially for pedestrians, followed by stab wound (89 cases, 32.1%) and falling injuries (32 cases, 11.6%), respectively. Haemothorax or pneumothorax (50.4%) and rib fracture (38.6%) were the most common types of chest injury. Extremity fracture was the most common associated injury with the rate of 37% ( 85/230), followed by head injury (25.2%) and abdominal trauma (19.6%). These injuries contributed significantly to the morbidity and mortality of trauma patients. According to the results, most patients with chest injury can be treated conservatively with close observation and tube thoracostomy. The presence of blunt trauma, head injury and abdominal injury independently adversely affect mortality after chest trauma. It is necessary to investigate the causes and patterns of injuries resulting from stab wound for effective prevention.


The impact of atherosclerosis and vascular collagen on energy-based vessel sealing.
Bipolar energy ligation of vessels in surgery is common. Although rare, serious failures occur. Atherosclerosis may contribute to seal failures by altering vascular compressibility and collagen content; however, no data exist. Femoral and iliac arteries of six Yucatan swine with an identified genetic locus predisposing them to atherosclerosis were denuded with a Fogarty catheter. Animals were fed a high-fat diet for 28 wk. A Yorkshire pig was used as a normal control and fed a standard diet. At 28 wk, arteries were measured for their diameters, sealed, and divided in vivo with LigaSure. The sealed artery sections were excised and subjected to burst pressure testing. Half of the seal distal to the aorta was kept intact for histology and collagen and elastin quantification. A multiple linear regression model was used to assess variables contributing to burst pressure. Covariates included were vessel diameter, degree of atherosclerosis, and collagen content. Experimental animals were hypercholesterolemic. Atherosclerosis occurred in 90% of seals in induced animals, with severe atherosclerosis in 62% of seals. There was site-selective deposition of atherosclerotic plaques in larger diameter iliac vessels. A model including collagen and size best predicted burst pressure. Every 10-U increase in collagen resulted in 15% increase in burst pressure (95% confidence interval = 0.2%-32%, P = 0.047, R(2) = 0.36). Atherosclerosis was unrelated to burst pressure controlling for collagen and size. Collagen and size provide the best model fit for predicting burst pressure. Quantitative research in human vasculature is warranted to better understand the influence of atherosclerosis and collagen content on seal failures.


Purification and characterization of an amylase from Opuntiaficus-indica seeds.
In Tunisia, prickly pear fruit grow spontaneously; it is consumed as fresh fruit, juice or jam. When the fruit is used for juice production, the seeds are discarded and go to waste. Our study aimed to extract biomolecules from seeds by producing value-added products from the fruits. An amylase from Opuntia ficus-indica seeds was extracted and purified to homogeneity. An increase in specific activity of 113-fold was observed. The apparent molecular mass of the enzyme is 64 kDa. The optimum pH and temperature for enzyme activity were pH 5 and 60 °C, respectively. Under these conditions, the specific activity is 245.5 U mg(-1) . The enzyme was activated by Co(2+) and Mg(2+) (relative activity 117% and 113% respectively) at lower ion concentrations. It was strongly inhibited by Mn(2+) and Fe(2+) . Cu(2+) inhibited totally the activity of this enzyme, but Ca(2+) has an inhibitory effect which increases with ion concentration. The extracted enzyme belongs to the exo type of amylases and is classified as a β-cyclodextrin glycosyltransferase since it generates mainly β-cyclodextrin from starch. It exhibits high thermal stability and a broad range of pH stability, making it a promising prospect for industrial and food applications.